Assessing the Biological Potency of Binary Mixtures of Environmental Estrogens using Vitellogenin Induction in Juvenile Rainbow Trout (Oncorhynchus mykiss)

Abstract

Experiments were conducted to assess the in vivo potency of binary mixtures of estrogenic chemicals using plasma vitellogenin (VTG) concentrations in juvenile rainbow trout (Oncorhynchus mykiss) as the endpoint. The estrogenic potencies of estradiol-17beta (E2), 4-tertnonylphenol (NP), and methoxychlor (MXC) were determined following 14 day exposures to the individual chemicals and binary mixtures of these chemicals. E2, NP, and MXC all induced concentration dependent increases in plasma VTG, with lowest observed effect concentrations of 4.7 and 7.9 ng L(-1) for E2, 6.1 and 6.4 microg L(-1) for NP, and 4.4 and 6.5 microg L(-1) for MXC. Concentration-response curves for fixed ratio binary mixtures of E2 and NP (1:1000), E2 and MXC (1:1000), and NP and MXC (1:1) were compared to those obtained for the individual chemicals, using the model of concentration addition. Mixtures of E2 and NP were additive at the concentrations tested, but mixtures of E2 and MXC were less than additive. This suggests that while NP probably acts via the same mechanism as E2 in inducing VTG synthesis, MXC may be acting via a different mechanism(s), possibly as a result of its conversion to HPTE which is an estrogen receptor alpha agonist and an estrogen receptor beta antagonist. It was not possible to determine whether mixtures of MXC and NP were additive using VTG induction, because the toxicity of MXC restricted the effect range forwhich the expected response curve forthe binary mixture could be calculated. The data presented illustrate that the model of concentration addition can accurately predict effects on VTG induction, where we know that both chemicals act via the same mechanism in mediating a vitellogenic response.

Interactions between estrogenic chemicals in binary mixtures investigated using vitellogenin induction and factorial analysis

“…Even though estrogenic chemicals tend to be present at low concentrations and exhibit weak activity individually, the potential exposure to mixtures of these chemicals suggests the possibility of additive and/or interactive effects, which could produce a significant combined response (Payne et al, 2000;Thorpe et al, 2001). In toxicology, depending on the presumed modes of action of the mixture's components, two concepts are used to predict the effects of mixtures: concentration addition (CA) and independent action (IA).…”

Distinct expression and activity profiles of largemouth bass (Micropterus salmoides) estrogen receptors in response to estradiol and nonylphenol

“…NP has also been shown to behave as a weak estrogen in a variety of standard in vitro tests including proliferation assays using the breast cancer MCF-7 cell line (Soto et al 1995, Blom et al 1998, Laws et al 2000, gene expression (Arukwe et al 2000a(Arukwe et al , 2001, Thorpe et al 2001), and recombinant reporter gene assays (Sohoni & Sumpter 1998, Yoon et al 2000. Previous reports demonstrate that NP binds directly to the estrogen receptor (ER) and subsequently induces transcription of downstream genes regulated by this pathway (Celius et al 1999).…”

Probing the xeno-oestrogenic impact of sediment cores contaminated by the pulp and paper industry: induction of aromatase cyp19a1b in late larval zebrafish

“…It was thus evident that of the two key biomarkers, vtg1 proved a robust indicator of mixture-induced effects. This goes along with studies using juvenile rainbow trout (Thorpe et al 2001), adult and embryonic fathead minnow (Brian et al 2005, Johns et al 2011 and juvenile zebrafish (Lin and Janz 2006). Theoretically, the joint effect of BPA + NP + OP (II) resulted in minimum additive response of the component chemicals.…”

“…This is due to biological effects with multiple components in an environmental mixture that may act unexpectedly regarding their combined capacity of impacts (Sumpter and Jobling 1995). Overall, estrogenic chemicals in mixtures may show a combination of effects in aquatic models (Thorpe et al 2001, Brian et al 2005, Lin and Janz 2006, Petersen and Tollefsen 2012.…”